The objective of this program is to study on a molecular basis the nature of the control of genetic activity. It is proposed to study such control on three levels, namely; the material nature of repressors, the nature of the unit genetic switching act by which the gene is repressed or derepressed and on the level of the genetic switching network, the way in which individual genetic switching units are linked together to bring about sequential developmental processes. It is proposed to attempt to achieve the desired objective by the use of a variety of methods; The study of the histones and other protein components of chromatin, physical studies of the interaction of repressor and DNA and of other protein components of chromosomes with DNA, chemical and physical studies of the basis of specificity between repressor and gene, physical studies of the structure of chromatin and in particular of its nuclear histone component, as well as physical and biochemical studies of the interaction of small molecules such as hormones and carcinogens with chromatin from appropriate target organs. It is proposed too to use in our attempts to achieve the desired objective, a variety of systems: the cellular slime mold, Drosophila, the varied organs of the rat and tissue cultured cells of rat and human. BIBLIOGRAPHIC REFERENCES: Bonner, J. Regulation of gene expression in higher organisms: how it works. Ciba Foundation Conference on Chromosome Structure and Function (Symposium) 28: 315-335, 1975. Douvas, A., C. Harrington, and J. Bonner. Major nonhistone proteins of rat liver chromatin. PNAS 72: 3902-3906, 1975.